EFFECTS OF CYCLIN-E OVEREXPRESSION ON CELL-GROWTH AND RESPONSE TO TRANSFORMING GROWTH-FACTOR-BETA DEPEND ON CELL CONTEXT AND P27(KIP1) EXPRESSION

Human tumors often display increased expression of cyclin E, suggestin g that this might contribute to their abnormal growth, However, we rep orted recently that overexpression of a human cyclin E cDNA in the non transformed mouse mammary epithelial cell line HC11 resulted in increa sed expression of the cell cycle-inhibitory protein p27(Kip1) and inhi bition of cell growth, To further address the role of cell context, in the present study we analyzed in parallel the effects of cyclin E ove rexpression in two fibroblast cell lines (Rat1 and NIH3T3) and three n ontumorigenic mammary epithelial cell lines (the human cell lines 184B 5 and MCF-10F and the mouse cell line HC11), This was associated with increased cyclin E-associated kinase activity in Rat1, NIH3T3, and MCF -10F cells but not in HC11 and 184B5 cells, The derivatives of the lat ter two cell lines showed increased expression of the p27(Kip1) protei n and inhibition of cell growth, There was a shortening of the G(1) ph ase in the derivatives of the Rat1 and MCF-10F cells but not in the de rivatives of the other three cell lines, Contrary to a previous hypoth esis, overexpression of cyclin E was not able to confer anchorage-inde pendent growth in any of these cell lines, However, overexpression of cyclin E was associated with increased resistance to transforming grow th factor beta-mediated growth inhibition in the 184B5 and HC11 cells and a decrease in transforming growth factor beta stimulation of the R at1 and NIH3T3 fibroblasts, Thus, overexpression of the same cyclin E cDNA has cell type-specific effects on various growth parameters, Ther efore, additional studies are required to better understand the signif icance of the frequent increase of cyclin E expression in human tumors .